Infectious microorganisms such as bacteria, fungi, algae, viruses, mildew, protozoa, and the like are capable of growing on a wide variety of living and non-living surfaces, including skin, teeth, mucosa, vascular tissue, medical implants, and medical devices. Invasive microbial infections of living organisms (e.g. bacterial, viral, protozoal, parasitic, fungal, etc.) can effect various organs of the body. Such infections are generally treated with well-characterized antimicrobial agents that may be safely tolerated by the host organism. However, the resistance of microorganisms to various antimicrobial agents has increased at an alarming rate rendering many important therapeutics for the treatment of microbial infections ineffective. Microorganisms employ one or more modes of resistance, often rendering them polyresistant. In particular, a great need still exists for effective antimicrobials for wound management and infections of the skin, oral mucosa and gastrointestinal tract. Individual microorganisms not attached to or growing on a surface are referred to as “planktonic”.
These planktonic organisms are responsible for invasive and disseminated infections in the host, when it is a living organism. Such planktonic organisms are the targets of conventional antimicrobial therapy.
When planktonic microorganisms grow and disseminate on non-living surfaces, they may cause contamination and biofouling of that surface. In many cases a microorganism can grow and accumulate on a surface to the point of becoming almost impossible to remove. This accumulation takes place through the formation of biofilms. A biofilm occurs when one or more microorganisms attach to a surface and secrete a hydrated polymeric matrix that surrounds them. Microorganisms existing in a biofilm, termed sessile, grow in a protected environment that insulates them from attack from antimicrobial agents. These sessile communities can give rise to nonsessile planktonic organisms, which rapidly multiply and disperse over the surface. Once again, it is these planktonic organisms that are the targets of conventional antimicrobial treatments such as antibacterial and antifungal agents. However, these conventional treatments fail to eradicate the sessile communities rooted in the biofilm. Biofilms are understood to be a frequently occurring reservoir for infectious agents and pose tremendous problems for the health-care industry. The biology of biofilms is described in more detail in Bacterial biofilms: a common cause of persistent infection” J. Costerson, P. Steward, E. Greenberg, Science 284: 1318-1322 (1999).
Microbial contamination and biofilms adversely affect the health care industry and other industries wherein microbial contamination poses a health risk to humans such as public water supplies, and food production facilities. Infections involving implanted medical devices, for example, generally involve biofilms, where a sessile community provides a reservoir for an invasive infection. Antibodies and host immune defenses are ineffective in killing the organisms contained in a biofilm even though these organisms have elicited the antibody and related immune response. Antibiotics typically treat the infection caused by the planktonic organisms, but fail to kill those sessile organisms protected in the biofilm. Therefore, even if the contaminated medical device were removed from the host, any replacement device will be particularly susceptible to contamination from the residual microorganisms in the area from which the medical device was removed.
Since the difficulties associated with eliminating biofilm-based infections and contamination are well-recognized, a number of technologies have developed to prevent or impair biofilm formation. These technologies include the development of various biocidal agents that are brought in contact with the contaminated or susceptible surface. However, any agent used to impair biofilm formation must be safe for use by humans and other non-target organisms. Biocides known to be effective at eliminating growth of unwanted microorganisms are generally toxic or otherwise harmful to humans, animals or other non-target organisms. Biocides known to be safe to non-target organisms, are generally less effective at preventing or eliminating microorganism growth, and require frequent application to the target surface.
Thus there is a need for antimicrobials that are safe, non-toxic, long-lasting and effective at controlling contamination and infection by unwanted microbial organisms, with minimal development of resistant or polyresistant microorganisms.